Curli are extracellular organelles produced by Escherichia coli and some Salmonella species. These fibers are structurally and biochemically identical to amyloid fibers in eukaryotic cells, according to a new research coming from the University of Michigan. Understanding how amyloid fibers are formed is important because these molecular structures are thought to be responsible for a wide range of diseases, including Alzheimer’s disease (AD), systemic amyloidosis, bovine spongiform encephalopathy (BSE; mad cow disease), and Creutzfeldt-Jacob disease, among others.
Biologist Matthew R. Chapman, PhD and colleagues are reporting in the latest issue of PNAS an “elegant model” of curli formation that might shed a light on our knowledge of amyloid diseases.A press release from the U of M is a fascinating read:

The research builds on a chance discovery that U-M microbiologist Matthew Chapman and co-workers made five years ago. In research initially aimed at understanding urinary tract infections [UTIs –ed.], they discovered that the common bacterium Escherichia coli makes and employs amyloid fibers, the same types of fibers that are the calling cards of many neurodegenerative diseases. Until then, amyloids were considered “biological blunders” that occurred only when proteins misfolded into deviant forms that aggregate into harmful clumps, Chapman said. But his work showed that bacteria produce amyloid fibers “by design” and use them to adhere to surfaces and to interact with other bacteria.
Since making the discovery, Chapman and his lab group have been exploring bacterial amyloids, using an approach that blends microscopy, biochemistry and genetics. In the current work, the researchers reveal details of how curli–functional amyloid fibers assembled by E. coli and certain other bacteria–are assembled.
In both bacteria and humans, amyloids form through a process known as nucleation, in which protein subunits link together in a coordinated fashion. Just as a snowflake begins as a speck of dust around which water freezes, an amyloid fiber also requires a template or nucleus to begin forming.
In bacteria, two proteins–CsgA and CsgB–are involved in the process, each with its own precise function. The job of CsgA is to build up amyloid fibers, but only after CsgB–dubbed “the nucleator”–has set the stage.
“What we’ve discovered is the molecular mechanism of bacterial amyloid nucleation,” said graduate student Neal Hammer, who is lead author on the paper. “The B protein presents an amyloid-like template to the A protein, which builds on that template to form a fiber.”
Having one protein in charge of nucleation and the other in charge of fiber elongation is a clever strategy that allows for control of a process that otherwise might occur unpredictably, as seems to happen with disease-associated amyloids.
“Control is achieved by keeping the A and B proteins apart until they get to the cell surface,” said Chapman, an assistant professor in the Department of Molecular, Cellular and Developmental Biology. “At the cell surface, they come together, resulting in controlled amyloid formation.”
Because CsgB speeds the amyloid fiber formation process, it prevents the buildup of potentially toxic intermediates, Chapman said. Similarly, studies of functional amyloids in other organisms have found that the fibers always form rapidly, bypassing intermediate steps. Such observations suggest new approaches to treating and preventing diseases such as Alzheimer’s.“Conventional wisdom has been that if we can prevent fiber formation, we can prevent these diseases,” Chapman said. “But if you think about what nature is telling us, it’s the exact opposite. I think what these functional amyloids are telling us is that maybe fiber formation is a process that should be happening, and that problems arise when the process goes too slowly and favors these toxic intermediates. Maybe what we should be doing is forcing the protein to form fibers in ways that skip the toxic intermediate steps.”